Within the Pacific Center for Marine Biomedicine this project will evaluate the biomedical potential marine microbes recovered from open ocean waters and marine biofilms. These will be brought into laboratory culture in the Core Facility for the Isolation and Characterization of Marine Microbes by using new approaches and technologies. The laboratory project will complement this effort through a comprehensive examination of biologically active small molecules that these microbes produce in laboratory culture. This effort is driven by the expectation that previously uncultured microbes will produce new chemistry with potential applications in biomedicine as lead compounds for drugs or pharmacological probes. Researchers participating in the present project have formed a multi-disciplinary team with expertise in the molecular biology of cancer, in neuroscience, and in natural product chemistry. In the cancer area we will be searching for small molecule modulators of the biological functions of oncoproteins, such as protein kinases involved in signal transduction cascades. In addition we will be searching for compounds with activity against the cytoskeleton, specifically microtubules and microfilaments. The screening for new anti-infectives will place emphasis on antibiotic activity against multi-drug resistant human pathogens as well as modulation of virulence factors of a common fungal pathogen. Lastly, we will search for new lead compounds with antioxidant properties that may serve as neuroprotective agents.